We will study the effects of some barbiturates and benzodiazepines on physical properties of mouse cell membranes, using electron paramagnetic resonance and fluorescence polarization techniques. We will see whether these drugs disrupt membrane organization, as ethanol does. The drugs will then be chronically administered to mice under conditions where tolerance and physical dependence can be demonstrated, and we will examine the membranes of chronically treated animals for changes in their responses to drugs administered in vitro, as well as for changes in chemical composition of the membrane lipids. We will study primarily plasma membranes, such as synaptosomal plasma membranes and erythrocyte ghosts. An anticonvulsant drug, sodium valproate, will also be studied, since we find that it resembles ethanol in membrane action (fluidization), in kinetics and in its CNS depressant action, and therefore might be a potential drug of abuse. The main drugs to be used here are pentobarbital, phenobarbital, oxazepam, and valproate.